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Association between low density lipoprotein receptor-related protein 2 gene polymorphisms and bone mineral density variation in Chinese population.

ABSTRACT: Low density lipoprotein receptor-related protein 2 gene (LRP2) is located next to the genomic region showing suggestive linkage with both hip and wrist bone mineral density (BMD) phenotypes. LRP2 knockout mice showed severe vitamin D deficiency and bone disease, indicating the involvement of LRP2 in the preservation of vitamin D metabolites and delivery of the precursor to the kidney for the generation of 1?,25(OH)(2)D(3). In order to investigate the contribution of LRP2 gene polymorphisms to the variation of BMD in Chinese population, a total of 330 Chinese female-offspring nuclear families with 1088 individuals and 400 Chinese male-offspring nuclear families with 1215 individuals were genotyped at six tagSNPs of the LRP2 gene (rs2389557, rs2544381, rs7600336, rs10210408, rs2075252 and rs4667591). BMD values at the lumbar spine 1-4 (L1-4) and hip sites were measured by DXA. The association between LRP2 polymorphisms and BMD phenotypes was assessed by quantitative transmission disequilibrium tests (QTDTs) in female- and male-offspring nuclear families separately. In the female-offspring nuclear families, rs2075252 and haplotype GA of rs4667591 and rs2075252 were identified in the nominally significant total association with peak BMD at L1-4; however, no significant within-family association was found between peak BMD at the L1-4 and hip sites and six tagSNPs or haplotypes. In male-offspring nuclear families, neither the six tagSNPs nor the haplotypes was in total association or within-family association with the peak BMD variation at the L1-4 and hip sites by QTDT analysis. Our findings suggested that the polymorphisms of LRP2 gene is not a major factor that contributes to the peak BMD variation in Chinese population.

SUBMITTER: Wang C

PROVIDER: S-EPMC3235174 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Association between low density lipoprotein receptor-related protein 2 gene polymorphisms and bone mineral density variation in Chinese population.

Wang Chun C Hu Yi-Ming YM He Jin-Wei JW Gu Jie-Mei JM Zhang Hao H Hu Wei-Wei WW Yue Hua H Gao Gao G Xiao Wen-Jin WJ Yu Jin-Bo JB Ke Yao-Hua YH Hu Yun-Qiu YQ Li Miao M Liu Yu-Juan YJ Fu Wen-Zhen WZ Ren Ying Y Zhang Zhen-Lin ZL

PloS one 20111209 12

Low density lipoprotein receptor-related protein 2 gene (LRP2) is located next to the genomic region showing suggestive linkage with both hip and wrist bone mineral density (BMD) phenotypes. LRP2 knockout mice showed severe vitamin D deficiency and bone disease, indicating the involvement of LRP2 in the preservation of vitamin D metabolites and delivery of the precursor to the kidney for the generation of 1α,25(OH)(2)D(3). In order to investigate the contribution of LRP2 gene polymorphisms to th ...[more]

PMID: 22174918

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Project description:BackgroundThe association between lipid and bone metabolism, particularly the role of high-density lipoprotein cholesterol (HDL-C) in regulating bone mineral density (BMD), is of significant interest. Despite numerous studies, findings on this relationship remain inconclusive, especially since evidence from large, sexually diverse Chinese populations is sparse. This study, therefore, investigates the correlation between HDL-C and lumbar BMD in people of different genders using extensive population-based data from physical examinations conducted in China.MethodsData from a cross-sectional survey involving 20,351 individuals aged > = 20 years drawn from medical records of health check-ups at the Health Management Centre of the Henan Provincial People's Hospital formed the basis of this study. The primary objective was to determine the correlation between HDL-C levels and lumbar BMD across genders. The analysis methodology included demographic data analysis, one-way ANOVA, subgroup analyses, multifactorial regression equations, smoothed curve fitting, and threshold and saturation effect analyses.ResultsMultifactorial regression analysis revealed a significant inverse relationship between HDL-C levels and lumbar BMD in both sexes, controlling for potential confounders (Male: β = -8.77, 95% CI -11.65 to -5.88, P < 0.001; Female: β = -4.77, 95% CI -8.63 to -0.90, P = 0.015). Subgroup and threshold saturation effect analyses indicated a stronger association in males, showing that increased HDL-C correlates with reduced lumbar BMD irrespective of age and body mass index (BMI). The most significant effect was observed in males with BMI > 28 kg/m2 and HDL-C > 1.45 mmol/L and in females with a BMI between 24 and 28 kg/m2.ConclusionElevated HDL-C is associated with decreased bone mass, particularly in obese males. These findings indicate that individuals with high HDL-C levels should receive careful clinical monitoring to mitigate osteoporosis risk.Trial registrationThe research protocol received ethics approval from the Ethics Committee at Beijing Jishuitan Hospital, in conformity with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are a contribution of the China Health Quantitative CT Big Data Research team, registered at clinicaltrials.gov (code: NCT03699228).

Dataset Information

Association between low density lipoprotein receptor-related protein 2 gene polymorphisms and bone mineral density variation in Chinese population.

Publications

Association between low density lipoprotein receptor-related protein 2 gene polymorphisms and bone mineral density variation in Chinese population.

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